Injection devices

ABSTRACT

Injection devices, such as needleless injection devices, and methods of making and using the same are disclosed.

REFERENCE TO RELATED APPLICATIONS

This application is a Divisional application of U.S. Ser. No.10/175,541, filed on Jun. 18, 2002, which is a Divisional application ofU.S. Ser. No. 09/465,573, filed on Dec. 17, 1999, now U.S. Pat. No.6,406,455, which claims the benefit of the filing date of U.S.Provisional application No. 60/112,805, filed on Dec. 18, 1998. Theentire content of the parent application U.S. Ser. No. 10/175,541 isincorporated by reference herein.

BACKGROUND OF THE INVENTION

The invention relates to injection devices and to methods of making andusing the same.

SUMMARY OF THE INVENTION

In general, the invention features, an injection device. The injectiondevice includes:

a gas chamber containing a gas or a source of gas;

a port which can allow for release of gas from said gas chamber;

a plunger, which upon the release of gas from said gas chamber, cancause movement of at least a first piston;

a first piston;

a second piston;

a first chamber, e.g. a chamber useful for drug storage and mixing;

a piston housing, in which are disposed said first piston, said secondpiston and said first chamber;

a displacement member which can, independent of the motive power of gasfrom said gas chamber, cause movement of one or both of the first andsecond pistons (the displacement member can be the plunger or a separatemember);

an orifice suitable for needleless injection in communication with saidfirst chamber;

wherein said first and second piston, are slideably disposed within saidpiston housing, and said displacement member, said source of gas, andsaid plunger are disposed such that:

in a first position of said pistons, a second chamber, e.g., a fluidreservoir, is defined within said piston housing by said first piston,said piston housing and said second piston,

said displacement member can move one or both of said pistons into asecond position wherein said first piston is in a position such thatsaid second chamber, which can be a fluid reservoir, is in communicationwith said first chamber, which can be a drug storage and mixing chamber,and said second piston is moved in the direction of the first piston,thereby decreasing the volume of the second chamber and allowing thetransfer of fluid from the second chamber to the first chamber,

said plunger, upon release of gas from the gas chamber, causes the firstpiston to move so as to decrease the volume of the first chamberallowing a substance to be expelled through the orifice and from saidchamber.

In a preferred embodiment the displacement member is activated manually.

In a preferred embodiment the displacement member is capable ofincremental movement, e.g., manually activated incremental movement, ofat least one of the pistons. By incremental is meant that the piston canbe displaced a certain amount, that displacement can be halted, but canthen be further displaced.

In a preferred embodiment a surface of the displacement member is incontact with a surface that is rigidly attached to the housing andfriction between the two surfaces allows for incremental movement, e.g.,manually activated incremental movement, of the displacement member withregard to the housing or of one of the pistons.

In a preferred embodiment a surface rigidly connected with thedisplacement member is in threaded contact with a surface that isrigidly connected with the piston housing and rotation between the twosurfaces allows for incremental movement, e.g., manually activatedincremental movement, of the displacement member with regard to thepiston housing or of one of the pistons.

In a preferred embodiment, the housing includes a bypass, e.g.,depressions in the wall of the housing, which when engaged by a piston,allows communication between the reservoir and drug storage and mixingchamber.

In a preferred embodiment the piston housing includes two subparts. Insuch embodiments one module, e.g., a storage and mixing or dry componentmodule, can supply the first piston, first chamber, and a part of thepiston housing and a second module occasionally, referred to herein as asecond component, or liquid component, module, can supply the secondchamber, second piston, and a part of the piston housing

The first, module can include a first module housing, the first pistondescribed above, a first module seal, and a first chamber defined by thefirst module housing said first piston' and optionally’ the first moduleseal.

The second component module can include a second component modulehousing, the second piston referred to above, a second module seal, anda second chamber defined by the second module housing, the secondpiston, and the second module seal.

In a preferred embodiment the modules include threads, components or abayonet closure, a storage module member and a fluid module member whichpresent frictional resistance to disengagement, or other means forholding the two modules together.

In a preferred embodiment engagement of the first module with the secondmodule enables communication between the first chamber, and the secondchamber.

In a preferred embodiment the first module includes a bypass, e.g., abypass which allows fluid to travel around or through the storage modulepiston. In a particularly preferred embodiment, the first module housingincludes a groove or passage which allows communication with the secondmodule. In another embodiment the first piston includes a hole (whichcan include a valve) which allows communication between the second andfirst chambers.

In a preferred embodiment one or both modules includes a piercing memberfor piercing one or both of the first module and second module seals.One or both of the seals can be disposed such that upon engagement ofthe second module with the first, one or both of the seals are pierced.This can enable communication between the first and second chambers.

A piercing member can engage one or both seals when the modules arebrought into close proximity and/or alignment. In a preferredembodiment, a piercing member can cut one or both seals as the threadsor other engaging members of the modules are brought into contact orotherwise operated. In a preferred embodiment a piercing member cuts byrotation of a seal relative to a piercing member. In another embodimentthe piercing member cuts by axial movement of a piercing member relativeto a seal. The cut made by a piercing member should be such that smallfragments of seal, which could enter the fluid chamber, are not formed.Free portions of seal should be of a size and location such that they donot enter the first chamber. In one embodiment, rotational motion of apiercing member relative to a seal can produce a cut portion or fragmentof the seal which is blocked by the first piston from entering the firstchamber. In another embodiment one or more portions or fragments of theseal remain attached to the housing after piercing.

In another embodiment, one or both seals are pierced by axialdisplacement of one or both pistons.

In another aspect, the invention, features a method of making aninjection device having disposed therein a substance, e.g., a drug,e.g., a lyophilized protein. The method includes:

providing the drug storage and mixing chamber of an injection devicedescribed herein;

and depositing the drug in the storage and mixing chamber.

In preferred embodiments the drug is lyophilized in situ in the drug inthe storage and mixing chamber.

In preferred embodiments the storage and mixing chamber is provided aspart of a first module, and an operation, e.g., filling orlyophilization, is performed: with the rest of the elements of theinjection device described herein present; without at least one of theother elements described herein, e.g., without the gas chamber present,or without at least one, or both, pistons present.

In preferred embodiments the storage and mixing chamber is provided aspart of a first module, and an operation, e.g., filling orlyophilization, is performed without at least one of the other elementsdescribed herein, e.g., without the gas chamber present, or without atleast one, or both, pistons present, and that element is added after theoperation.

In preferred embodiments the liquid chamber is provided as part of asecond module, and an operation, e.g., filling or sterilization, isperformed: with the rest of the elements of the injection devicedescribed herein present; without at least one of the other elementsdescribed herein, e.g., without the gas chamber present, or without atleast one, or both, pistons present.

In preferred embodiments the liquid chamber is provided as part of asecond module, and an operation, e.g., filling or sterilization, isperformed without at least one of the other elements described herein,e.g., without the gas chamber present, or without at least one, or both,pistons present, and that element is added after the operation.

In preferred embodiments, after deposit or lyophilization, one or moremoisture resistant seals, e.g., a metal or polymer seal, are applied tothe storage and mixing chamber.

In another aspect, the invention features, a piston housing having twosubparts, for use with an injection device. The piston housing includestwo modules: a first module which can contain a first substance, e.g.,preferably a substance other than a liquid, e.g., a solid, e.g., a dryor lyophilized protein; and a second module, which can contain a secondsubstance, e.g., a fluid or solute.

The first module, which can, e.g., be a storage and mixing module, caninclude a first module housing, a first module piston, e.g., the firstpiston described elsewhere herein, a first module seal, and a firstchamber defined by the first module housing, said first piston, and thefirst module seal.

The second module can include a second module housing, a piston, e.g.,the second piston referred to elsewhere herein, a second module seal,and a second chamber defined by the second module housing, the piston,and optionally the second module seal.

In a preferred embodiment the modules include threads, components or abayonet closure, a first module member and a second module member whichpresent frictional resistance to disengagement, or other means forholding the modules together.

In a preferred embodiment engagement of the second module with the firstmodule enables communication between the second chamber and the firstchamber.

In a preferred embodiment the first module includes a bypass, e.g., abypass which allows fluid (e.g., from the second module chamber) totravel around or through the first module piston. In a particularlypreferred embodiment, the first module housing includes a groove orpassage which allows communication with the second module. In anotherembodiment the first piston includes a hole (which can include a valve)which allows communication between the second and first chambers.

In a preferred embodiment one or both modules includes a piercing memberfor piercing one or both of the first module and second module seals.One or both of the seals can be disposed such that upon engagement ofthe second module with the first, module, one or both of the seals arepierced. This can enable communication between the first and secondchambers.

A piercing member can engage one or both seals when the modules arebrought into close proximity and/or alignment. In a preferredembodiment, a piercing member can cut one or both seals as the threadsor other engaging members of the modules are used to engage the modules.In a preferred embodiment a piercing member cuts by rotation of a sealrelative to a piercing member. In another embodiment the piercing membercuts by axial movement of a piercing member relative to a seal. The cutmade by a piercing member should be such that small fragments of seal,which could enter the fluid chamber, are not formed. Free portions ofseal should be of a size and location such that they do not enter thefirst chamber. In one embodiment, rotational motion of a piercing memberrelative to a seal can produce a cut portion or fragment of the sealwhich is blocked by the first piston from entering the first chamber. Inanother embodiment one or more portions or fragments of the seal remainattached to the housing after piercing.

In another embodiment, one or both seals are pierced by axialdisplacement of one or both pistons.

In preferred embodiments the storage and mixing chamber is provided aspart of a first module, and an operation, e.g., filling orlyophilization, is performed: with the rest of the elements of thepiston housing present; without at least one of the other elementsdescribed herein, e.g., without the second module.

In preferred embodiments the liquid chamber is provided as part of asecond module, and an operation, e.g., filling or sterilization, isperformed: with the rest of the elements of the piston housing present;without at least one of the other elements described herein, e.g.,without the first module.

In preferred embodiments, after deposit or lyophilization, one or moremoisture resistant seals, e.g., a metal or polymer seal, are applied tothe storage and mixing chamber.

The invention also features a method of providing a first and secondcomponent by providing the components in the modules described herein.

The invention also features a kit which includes one or more of: one orboth of the modules described herein, e.g., a storage module containinga first component, e.g., a dry component, and/or a fluid modulecontaining a second component, e.g., a diluent; instructions for use,and other elements of the injectable device described herein.

In order to reconstitute a drug disposed within a syringe many currentdesigns of bypass syringes require that the patient to push the syringepiston forward in order to initiate flow of diluent into the lower partof the syringe containing the lyophilized drug. There is a certainamount of friction (sticksion) to be overcome in order to move the butylrubber piston forward. Unless the patient has very good manual dexterity(which is not always the case) it is natural to apply too much pressureon the syringe piston. This action may lurch the piston forward whichmay result in overflow of diluent and drug out the end of the syringe.The syringes described herein minimize this problem.

Syringes disclosed herein, having two separate chambers which bymechanical means (e.g., threaded mating parts) provides a more foolproofaction, with a mechanical advantage, that overcomes the sticksionproblem.

The modular chamber-containing elements of the invention allow forflexible manufacturing, distribution, and use of medications whichrequire mixing of two components.

Other features and advantages of the invention will be apparent from thefollowing detailed description, and from the claims.

DETAILED DESCRIPTION DRAWINGS

The drawings are first briefly described.

FIG. 1 is a diagram of an embodiment of an injectable device.

FIG. 2 is a diagram of an embodiment of an injectable device.

FIG. 3 is a diagram of an embodiment of an injectable device.

FIG. 4 is a diagram of an embodiment of an injectable device.

FIG. 5 is a diagram of an embodiment of a first module which can be usedin a device described herein. The module includes a chamber which can beused to contain a dry component.

FIG. 6 is a diagram of an embodiment of a second module which can beused in a device described herein. The module includes a chamber whichcan be used to contain a liquid component.

FIG. 7 is a diagram of an embodiment of a first module an embodiment ofa second module in an engaged position.

FIG. 8 is a diagram of an embodiment of a first module an embodiment ofa second module.

FIG. 9 is a diagram of an embodiment of a first module an embodiment ofa second module in an initial phase of an engaged position.

FIG. 10 is a diagram of an embodiment of a first module an embodiment ofa second module in a completely engaged position.

NEEDLELESS SYRINGE

Referring to FIG. 1, an embodiment of a syringe includes three sectionsherein referred to as lower (1), middle (2), and upper (3). With theexception of the moisture resistant, e.g., metal foil, seals, spring (5)and compressed gas reservoir (6), all the other parts can bemanufactured by plastic injection molding.

The lower section includes cylindrical housing (1), further defined byorifice (13), cap 13 a, and one or a plurality, e.g., three or four,evenly spaced grooves (12) on the inside of (1) at the end facing piston9 a. The space (13 b) within (1) is reserved for lyophilized drug (14).

The middle section is characterized by cylindrical housing (2) having anexterior thread (2 a) and is further defined by a fluid reservoir (15)containing an aqueous diluent (15 a). Fluid reservoir (15) is bounded bytwo pistons, e.g., rigid pistons having elastomeric seals or elastomericpistons (9 a,b) having metal foil seals on the outside aspect of housing(2).

Housing (2) may be manufactured separately from housing (1) such that itcan be further characterized by a vapor deposited metal film on itsouter surface. (Vapor barrier metalization is desirable if the materialdoes not have a suitable vapor transmission characteristics.) Housing(1) and (2) must be securely mated at the time of assembly. This 2-partassembly allows for visual inspection of the mixing of diluent (15 a)with lyophilized drug (14) while at the same time providing a vaportransmission barrier around the contained diluent (15). The metallizedvapor barrier consisting of the metal foil seals on the outer ends ofplungers (9 a,b) and the coating on the outside of housing (2) will aidin ensuring a long shelf-life for the product. In addition to glass,metal foils and coatings offer the best protection against water vaportransmission. Since the syringe assembly will be packaged in a foilpouch, any water vapor escaping from the diluent reservoir willaccumulate within the air inside the foil pouch. This accumulated watervapor may have an adverse effect on the stability of the lyophilizeddrug. This can be prevented or greatly reduced by the all encompassingmetal barrier surrounding diluent reservoir (15).

The upper section includes cylindrical housing (3) having floatingplunger (10), a space (11), fixed actuator (4), spring (5), compressedgas reservoir (6), release button (7) and detents (16). Housing (3) isfurther characterized by a thread (3 a) on the inside of the housingwhich mates with that (2 a) on the outside of middle section (2).

Referring to FIGS. 2, 3, and 4, use of the device is described. Thedevice is removed from its foil pouch. The foil seal is removed fromhousing (1) and assembled with housing (2). (In some embodiments thefoil seal is pierced automatically when the chambers are engaged.)Holding the syringe assembly in the vertical position with orifice 13pointing up, grasp the lower section (2) (end facing up) with one handand with the other rotate housing (3) around housing (2). This actionresults in floating plunger (10) pushing against plunger (9 b) therebypushing diluent column (15 a) and plunger (9 a) into the space definedby grooves (12). Pistons 9 a and 9 b are under radial compression. Sinceplunger (9 a) is under compression when assembled, it expands when itenters the space surrounding grooves (12) thereby providing resistanceto further movement. This is depicted in FIG. 2. The hydraulic couplingbetween the two pistons 9 a and 9 b is removed once the piston 9 a ispositioned with the grooves around it allowing the fluid to transfer tochamber (1). As housing (3) is further rotated, diluent (15 a) flows bypiston 9 a through grooves (12) and into space (13 b) containinglyophilized drug (14) until all the diluent is pushed into housing (1)at which time housing (3) reaches the end of its travel (e.g.,approximately ¾ turn, the amount of rotation can vary, e.g., on thethread pitch selected). This is depicted in FIG. 3. The air displaced bydiluent (15 a) escapes through the hydrophobic vent in cap (13 a). Inthis position piston 9 a and 9 b have made contact and jointly form aseal over the fluid transfer slots.

The syringe assembly is rocked in a back and forth motion until the drugis totally dissolved and thoroughly mixed with diluent (15 a).

To inject the drug into the body, cap 13 a is removed and while holdingthe syringe assembly in the vertical position, orifice 13 is pressedagainst the skin. The thumb is then used to press injection button (7).This action locks the button in position at detents 16, actuator (4)seats against the chamfered end of opening 11. When gas reservoir (6)hits the pointed end of the actuator (4), a seal is ruptured inreservoir (6) thereby releasing the compressed gas contained therein.The gas escapes through actuator (4) and into opening (11) where itimpinges upon the bottom of floating plunger (10). Plunger (10) pushesagainst mated pistons (9 a,b) (see FIG. 3) thereby expelling the drugthrough orifice 13 and into the skin. The entire injection process iscomplete less than 2 seconds. The final position of the pistons isdepicted in FIG. 4. At this point, the injection is complete and thesyringe is ready for disposal.

Actuator (4), radial slots (11 a) and orifice (13) as well as thematerial surrounding and defining opening 11 can be designed so as tooptimize the pressure profile. The interface between the outside surfaceof the fixed cylinder (11) and the inside plunger (10) can be configuredto optimize the pressure profile during the injection phase. Devices inthe art have used a variety of pressure profiles. While not wishing tobe bound by a particular theory or approach, one potential profile caninclude an initial high-pressure spike. (−4000 psi) of very shortduration (on the order of milliseconds) which creates a channel throughthe skin. The high-pressure spike is followed by a rapid fall inpressure to a constant level (−2,000 psi). This pressure is sufficientto keep the skin channel open and to allow for drug flow through thechannel and into the body.

In another embodiment, the gas pressure can be generated by a chemicalreaction similar to that found in automobile air bags. This chemicalreaction is extremely fast and efficient and creates a source ofhigh-pressure nitrogen gas.

As is discussed below, the chambers which hold the two substances can beprovided by separate modules. The lower (1) and middle (2) sections ofFIG. 1 can be replaced with the modular components described herein.

Modular Systems

Devices of the invention can include separate modules for a firstcomponent, e.g., a dry component, and a second component, e.g., a liquidcomponent. The modules can be provided as two separate components andassembled, e.g., by the subject who will administer the component tohimself or herself, or by another person, e.g., by an individual whoprovides or delivers health care. Together, the modules can form all orpart of the piston housing of devices described herein. E.g., they cansupply (1) the lower and middle (2) sections of FIG. 1. In suchembodiments one module, referred to herein as a second component orliquid component module, can supply the second chamber, second piston,and a part of the piston housing, and a second module, referred toherein as a storage and mixing, or dry component module, can supply thefirst piston, first chamber, and a part of the piston housing. Althoughthe description provided herein refers to a liquid component and alyophilized or other dry component it will be understood that themethods and devices can be used to provide any first and secondcomponent where it is desirable to store or provide the componentsseparately and combine them prior to administration to a subject.

FIG. 5 is a diagram of an embodiment of a first module (20) whichincludes first module housing (21) having an orifice (22), fluid bypasspassages (23), threads (24) for engagement with a second module, and apiercing element (25). Piston (26) is disposed within first modulehousing (20). First module seal (27) is disposed so as to preventcontact of the atmosphere with the chamber (28). Cap (29) covers orifice(22) and protects it until use. A dry substance, e.g., a lyophilizedprotein can be disposed within chamber (28).

FIG. 6 is a diagram of an embodiment of a second module (30) whichincludes second module housing (31), threads (32) for engagement with afirst module, and a piercing element (33). Piston (34) is disposed onsecond module housing (30). Second module seal (35) is disposed so as toprevent contact of the atmosphere with the chamber (36). A liquidsubstance, e.g., a diluent or carrier, can be disposed within chamber(36).

FIG. 7 is a diagram of an embodiment of an assembled piston housing unit(40) which includes a first and second module. The assembled pistonhousing unit can be used with the injectors described herein. As shown,the engaged first and second module is then engaged with othercomponents of the unit. However, assembly is not limited to thissequence, e.g., the second module can be combined with other elementsand then engaged with the first module.

When the modules are incorporated into the assembled injector movementof second piston (34) in the direction of first piston (26) causes thecontents of chamber (36) to enter chamber (28), by way of bypass (23).Travel of piston (26) so as to reduce the volume of chamber (28) resultsexpulsion of the contents of chamber (28) through orifice (22).

In the embodiment described in FIG. 7, piston (26) is disposed such thatit need not be moved relative to bypass (23) to allow communication ofchamber (36) with chamber (28).

In other modular embodiments, piston (26) and bypass (23) are disposedanalogous to the pistons shown in FIG. 1, i.e., disposed relative to oneanother such that piston (26) must be displaced to allow communicationsbetween chamber (36) and chamber (28).

FIGS. 8, 9, and 10 show another embodiment of a modular device.

FIG. 8 is a diagram of an embodiment of a first module (60) and secondmodule (50). First module (60) includes first module housing (61) havingan orifice (62), fluid bypass passages (63). Piston (64) is disposedwithin first module housing (60). First module seal (65) is disposed soas to prevent contact of the atmosphere with the chamber (66). A drysubstance, e.g., a lyophilized protein can be disposed within chamber(66). Also shown is a second module (50) which includes second modulehousing (51) and piston (52) which is disposed in second module housing(50). Second module seal (53) is disposed so as to prevent contact ofthe atmosphere with the chamber (54). A liquid substance, e.g., adiluent or carrier, can be disposed within chamber (54).

FIG. 9 is a diagram of an embodiment of a first module an embodiment ofa second module in an initial phase of an engaged position. Piercingelements (67) have not yet pierced seals (68).

FIG. 10 is a diagram of an embodiment of a first module an embodiment ofa second module in a completely engaged position. Piercing elements (69)have pierced seals (70) allowing communication between chambers (71) and(72).

Operation of modular embodiments is otherwise analogous to thatdescribed for the embodiment shown in FIG. 1.

Use

The invention provides for the delivery of a mixture of two substancesfrom the first chamber, a first substance originally held in the firstchamber and a second substance originally held in the second chamber buttransferred into the first by operation of the device. The firstsubstance can be a dry substance, e.g., a lyophilized protein, nucleicacid, e.g., RNA or DNA, or polysaccharide. The first substance can be avaccine, or a drug. The first substance can be a peptide, polypeptide,or protein, e.g., an antibody, an enzyme, a hormone or growth factor.Particularly preferred first substances include insulin.

The first substance can be: a blood protein, e.g., clotting factor VIIIor a IX, complement factor or component; a hormone, e.g., insulin,growth hormone, thyroid hormone, a catecholamine, a gonadotrophin, PMSG,a trophic hormone, prolactin, oxytocin, dopamine and the like; a growthfactor, e.g, EGF, PDGF, NGF, IGF's and the like; a cytokine, e.g., an,interleukin, CSF, GMCSF, TNF, TGF-alpha, TGF-beta. and the like; anenzyme, e.g., tissue plasminogen activator, streptokinase, cholesterolbiosynthetic or degradative, glycosolases, and the like); a bindingprotein, e.g., a steroid binding protein, a growth hormone or growthfactor binding protein and the like; an immune system protein, e.g., anantibody, SLA or MHC gene or gene product; an antigen, e.g., abacterial, parasitic, or viral, substance or generally allergens and thelike. The second substance can be a liquid, e.g., a diluent or solute.Such liquids can include buffers, inert fillers, pharmaceuticallyacceptable carriers, or the like.

The subject can be a human or an animal, e.g., a laboratory animal, orpet, e.g., a dog or cat, or other animal, e.g., a bovine, a swine, agoat, or a horse. The first and second substance can be combined by thesubject, or by another person.

Formation of the Orifice

The size and shape of the orifice on the end of the syringe is importantnot only for obtaining the proper pressure profile, but also forminimizing or eliminating the possibility of protein shearing when usingprotein based drugs. This means the orifice must have a very smoothsurface. Typically, shearing off a gate on the end of the syringe formsthe orifice. This may result in a jagged edge, which can shear proteins.It is preferred to provide an orifice with edges which are sufficientlysmooth such that protein shearing is minimized, e.g., an orificesufficiently smooth such that after passage through the orifice innormal use a protein drug, e.g., insulin, retains at least, 40, 50, 60,70, 80, 90, or 95% of a biological activity. A pin in the mold, or morepreferably, laser machining, can be used to form the orifice. Lasermachining, in particular, forms a very precise hole having a smoothsurface.

Deposit of Drug

The lower section of the syringe (1 in drawing) can be used as alyophilization chamber. Upon completion of lyophilization, a metal foilseal will be bonded over the end of chamber (1) where it mates withchamber (2). The end of chamber (2) will also have a bonded foil seal.The product will come in two or three parts. The user can remove thefoil seals from chambers (1) and (2) and connect them together by meansof a snap lock, mechanism. In other embodiments the action of thechambers being connected will automatically shear the seals and containthem is a manner so as not to allow entry of portions of seal into thefirst chamber. The combined piece will then be threaded into the upperchamber (3) having the plunger means and actuator.

In modular embodiments, the drug is deposited in the storage chamber(see chamber (28) of FIG. 5 and FIG. 7).

Other embodiments are within the following claims.

1. A piston housing having two modules, for use with an injectiondevice, said housing comprising: (1) a first module comprising: a firstmodule housing, a first piston, a first module seal, and a first chamberdefined by said first module housing, said first piston, and said firstmodule seal; and (2) a second module comprising: a second modulehousing, a second piston, a second module seal, and a second chamberdefined by said second module housing, said second piston, and saidsecond module seal; wherein said first module is capable of engagingsaid second module such that said first module seal is disposed proximaland adjacent to said second module seal.
 2. The injection device pistonhousing of claim 1, wherein engagement of said first module with saidsecond module enables communication between said first chamber and saidsecond chamber.
 3. The injection device piston housing of claim 1,wherein one or both modules comprises a piercing member for piercing oneor both of said first module seal and said second module seal.
 4. Theinjection device piston housing of claim 1, wherein one or both of saidfirst and second module seals are disposed such that upon engagement ofsaid first module and said second module, one or both of said seals arepierced to allow communication between said first chamber and saidsecond chamber.
 5. The piston housing of claim 1, wherein said firstmodule further comprises an orifice configured for needless injection.6. The piston housing of claim 5, wherein said orifice is covered by aremovable cap until use.
 7. The piston housing of claim 1, wherein saidfirst module further comprises one or more fluid bypass passages thatallow fluid communication between said first chamber and said secondchamber.
 8. The piston housing of claim 7, wherein said first piston isdisposed such that it need not be moved relative to said fluid bypasspassages to allow communication of said first and said second chambers.9. The piston housing of claim 7, wherein said first piston is disposedsuch that it must be displaced relative to said fluid bypass passages toallow communication of said first and said second chambers.